Delivery of inhaled medication in children
Robert H Moore, MD
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INTRODUCTION — The delivery of aerosolized medication is an important component of treatment
for many respiratory disorders, and is a critical aspect of asthma management in children.
Corticosteroids, bronchodilators, antibiotics, and mucolytic agents can be administered via aerosol
using a range of aerosol generating devices [1-4]. In addition, as novel macromolecular medications
are delivered via the respiratory tract for the treatment of both pulmonary and systemic disorders,
indications for aerosol therapy will broaden [5,6]. (See "Delivery of inhaled medication in adults").
The delivery of aerosolized medication to infants and children is complicated by anatomic and
physiologic differences in their respiratory systems [7-9]. Thus, a basic knowledge of the uses and
limitations of aerosol delivery systems, the properties of effective aerosols, and the anatomic
considerations affecting aerosol delivery in infants and children is essential to the optimal use of this
therapeutic modality [10,11]. An overview of the delivery of inhaled medication in children will be
presented here; specific aspects of medication delivery using nebulizers, pressurized metered dose
inhalers, and dry powder inhalers are discussed separately. ( See "Use of medication nebulizers in
children" and see "Use of metered dose and dry powder inhalers in children").
Advantages of drug delivery by aerosols versus systemic drug delivery include:



effect.
Delivery of agents directly to their sites of action decreases the dose required for therapeutic
Faster onset of action (compared to intravenous delivery) of bronchodilating medications
allows more rapid reversal of acute bronchoconstriction.
Reduced systemic bioavailability minimizes side effects.
Three types of aerosol delivery devices are widely employed in the management of children with
respiratory disease (show table 1A-1B):



Nebulizers, which use a jet flow of driving gas or ultrasound to aerosolize medications
Pressurized metered dose inhalers
Dry powder inhalers
Specific issues related to the use of these devices are discussed separately. ( See "Use of medication
nebulizers in children" and see "Use of metered dose and dry powder inhalers in children").
Lung diseases managed using aerosol therapy — A wide range of pediatric disorders can be treated
effectively using aerosol therapy as a central component of management. Examples include:

Obstructive airway diseases, including asthma, congenital emphysema, bronchiectasis, and
bronchiolitis

Processes that result in acute upper airway obstruction, usually croup or postextubation
upper airway edema


Chronic lung diseases, including bronchopulmonary dysplasia and cystic fibrosis
Infectious diseases, including Pneumocystis jiroveci pneumonia (treatment and prophylaxis),
respiratory syncytial virus infection, and some pulmonary fungal infections [12-15].
Less common indications for aerosol therapy include intractable cough, which may respond to
inhaled lidocaine and administration of analgesia in the setting of palliative care, using inhaled
morphine. In the future, aerosol delivery of gene constructs could be an important component of
therapy for genetic diseases [5].
Properties of an ideal aerosol therapy device — The ideal aerosol delivery device varies depending
on the medication to be administered and the clinical situation. To maximize the advantages of
inhaled medications described above, the device selected should:





Deliver an adequate dose of medication to the lungs
Minimize oropharyngeal deposition and systemic side effects
Match the needs of the patient
Be simple for the patient to use
Be cost effective
FACTORS AFFECTING DRUG DEPOSITION — A number of factors influence the ultimate amount of
medication delivered to the appropriate anatomic region within the lung.
Properties of the device — Devices vary greatly in their efficiencies in delivering particles to the
lungs. From 6 to 60 percent of the total dose of medication is delivered to the peripheral airways
when these devices are used optimally [16]. (See "Delivery of inhaled medication in adults").
Aerosol properties — Aerosol particles are characterized by their mass median aerodynamic
diameter (MMAD) [17,18]. Particles with a MMAD between 2 and 5 µm are optimal for deposition in
the lower airway, and are deposited largely by inertial impaction with airway structures.
Particles with MMAD of 0.8 to 2 µm are optimal for alveolar deposition, which occurs largely as a
result of gravitational sedimentation [7,19]. Particles with a MMAD greater than 5 µm are deposited
largely in the oropharynx, while those less than 1 µm generally are exhaled.
Properties of medication to be delivered — The ultimate effect of the dose is dependent on the site
of deposition of the drug within the lung, the rate of drug clearance from the airway, and the site of
action of the medication [16]. To be effective, drugs must be able to withstand the shear forces
required to generate the aerosol, and often must penetrate the mucous layer and airway mucosa to
reach their target receptors or cells [5].
Disease state and ventilatory pattern — Anatomic and pathologic factors, as well as ventilatory
patterns, alter the efficiency of aerosolized drug delivery. In diseases that are associated with
decreased airway caliber, such as asthma, aerosol particles may be deposited in the central airways.
In infants with acute bronchiolitis, the targeting of aerosol particles to the appropriate airways may
be further compromised, with only 1.5 percent of aerosolized drug released from the nebulizer being
deposited in the lung, and 0.6 percent penetrating to the peripheral airways [ 20].
Diseases causing mucous plugging or atelectasis, such as cystic fibrosis, may lead to reduction and
marked heterogeneity in the distribution of particle deposition. Other factors such as tidal volume,
breath-hold time, respiratory rate, and nose versus mouth breathing can dramatically alter the
deposition of aerosolized particles in the lungs [7,21].
Patient technique, acceptance, and preference — Improper technique is a common cause for a
suboptimal response to aerosolized medication, and poor understanding or acceptance may lead to
noncompliance. Rapid inspiration may increase inertial impaction of droplets in the central airways
and decrease lung delivery [21]. Patient education is essential for the effective use of any aerosol
delivery device [1]. Further, patient factors such as weakness, severe arthritis or contractures, and
altered mental status may mandate the use of specific delivery devices. ( See "Patient information:
Overview of managing asthma" and see "Patient information: Metered dose inhaler techniques").
SPECIAL CONSIDERATIONS IN INFANTS AND YOUNG CHILDREN — The deposition of medication in
peripheral airways and alveoli is reduced in infants and young children, presumably due to their
smaller airways, faster respiratory rates, and lower tidal volumes, which combine to lower the
resident time of small particles in the airway [7-9,22,23].
Dosage — There are data that suggest that drug deposition in children over the age of five to six
years is similar to that observed in adults, and that identical doses in children and adults result in
similar plasma concentrations [16,24]. In general, aerosol doses do not need to be decreased except
possibly in very young children; however, it is probable that variability exists based on the specific
medication and delivery device employed.
For children less than six months of age, the inspiratory flow rate may be exceeded by the output of
the aerosol generating device, resulting in the loss of air entrainment and a higher concentration of
drug in the aerosol. Overall, this effect can lead to a higher inhaled dose per kilogram of body weight
in the infant less than six months of age, increasing the possibility of side effects [ 23].
Respiratory pattern — Crying markedly reduces aerosol delivery to the lungs, and in general,
aerosols should not be administered to crying children [25,26]. While normal tidal breathing results
in the most efficient delivery to the airways, it is preferable to administer aerosols to sleeping infants
and children as compared to those who are crying.
Breath-actuated devices and dry powder inhalers should be avoided in infants and toddlers, due to
their inability to generate an adequate inspiratory flow rate to reliably aerosolize the medication
[16]. (See "Use of metered dose and dry powder inhalers in children").
Interface — The interface between the aerosol generating device and the patient is an important,
and often overlooked, component of effective therapy. Whenever possible, administration of aerosols
by a mouthpiece over a facemask is preferable due to improved drug delivery to the lungs by as
much as twofold [27]. However, delivery by facemasks or mouthpieces has been shown to provide
similar clinical responses when administering bronchodilators in children with acute asthma [ 28] or
nebulized budesonide in chronic asthma [29].
Poor patient cooperation leads many parents to use blow-by techniques for aerosol delivery.
However, removing the facemask just 1 cm from the face reduces the inspired dose by
approximately 50 percent, and a 2 cm distance results in an 80 percent reduction [21]. When a
facemask is used, it should be placed snugly over the face.
The nose is an efficient filter for particles in aerosol; thus, when using a facemask, any nose
breathing will be associated with increased deposition in the upper airway [ 21,30]. This may lead to
more systemic side effects, due to greater drug absorption from the upper airway. In addition, this
can reduce drug efficacy because of decreased deposition in the lower respiratory tract [ 1,28].
Specific aspects of aerosolized medication delivery using nebulizers, metered dose inhalers, and dry
powder inhalers are presented separately. (See "Use of medication nebulizers in children" and see "Use of
metered dose and dry powder inhalers in children").
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GRAPHICS
Comparison of aerosol devices
Comparison of pMDI with holding chamber, DPIs, and nebulizers as aerosol delivery devices
pMDI/HCDPIsNebulizer
Performance
Majority of aerosol particles <5 µm in size +
+
±
High pulmonary deposition
+
±
±
Low mouth deposition
+
±
-
Reliability of dose
+
±
±
Influenced by humidity
-
+
-
Physical and chemical stability
+
+
+
Breath actuated
-
+
-
Risk of contamination
-
-
+
Lightweight, compact
+
+
-
Multiple doses
+
+
-
Dose indicator
-
+
-
Dose counter
-
+
-
Inexpensive
+
+
-
Easy and quick operation
±
±
-
Suitable for all ages
+
-
+
Suitable for multiple clinical situations
+
±
+
Convenience
DPI: dry power inhaler; pMDI: pressurized metered-dose inhalers.
Reproduced with permission from: Rubin, BK, Fink, JB. Aerosol therapy for children. Respir
Care Clin N Am 2001; 7:175. Copyright © 2001 Elsevier Science (USA).
Aerosol device comparison
Advantages and disadvantages of various aerosol devices
Type
Jet nebulizer
Advantages
Patient coordination not
required
High doses possible
No CFC release
Disadvantages
Expensive
Not portable - pressurized gas source
required
More time required
Contamination possible
Device preparation required before
treatment
Not all medications available
Less efficient than other devices (dead
volume loss)
Ultrasonic nebulizer
Patient coordination not
required
Expensive
Contamination possible
High doses possible
Prone to malfunction
No CFC release
Not all medication available
Small dead volume
Quiet
Device preparation required before
treatment
No drug loss during
exhalation
Faster delivery than jet
nebulizer
Metered-dose inhaler
Convenient
Patient coordination essential
Less expensive than
nebulizer
Patient actuation required
Large pharyngeal deposition
Portable
Difficult to deliver high doses
More efficient than
nebulizer
No drug preparation
required
Many use CFC propellants
Not all medications available
Difficult to contaminate
Metered-dose inhaler with
holding chamber
Less patient coordination
required
More complex for some patients
More expensive than MDI alone
Dry powder inhaler
Less pharyngeal
deposition
Less portable than MDI alone
Less patient coordination
required
Requires moderate to high inspiratory
flow
Convenient
Some units are single dose
Can result in high pharyngeal
Breath-hold not required
deposition
Propellant not required
Not all medications available
Portable
Difficult to deliver high doses
Breath-actuated
CFC: chlorofluorocarbon; MDI: metered-dose inhaler.
From Consensus Statement: Aerosols and Delivery Devices. Respir Care 2000; 45:589.